4-amino-2-hydroxypyrimidine

Reductive animation of 2-acetamido-5-amino-4-hydroxypyrimidine, readily available from isocytosine via nitration, acetylation and reduction, with (299) generated (300), which was characterized as the crystalline bisformamide (301). Mild acid hydrolysis effected cleavage of all three amide bonds to afford (302), which was hydrolyzed to (303) under slightly more vigorous conditions. 

The solubility of (S) 3,5-dichloro-2-hydroxy-[[2-[[[3-hydroxy-5[l, 4,5,6-tetrahy-dro-5-hydroxypyrimidin-2-yl-amino]phenyl]carbonyl]amino]acetyl]amino]-benzene-propanoic acid and its monohydrate was measured at several temperatures in different aqueous acetonitrile solvent systems [7]. The data were fitted to a frame-... 

Hydroxypyrimidines have been detected in the Murchison, Murray, and Orgueil carbonaceous chondrites in abundances similar to those of amino acids [7]. Earlier analyses of the Orgueil meteorite By thin layer chromatography of organic extracts indicated the presence of melamine, ammeline, adenine, and guanine [8]. Although these could not be confirmed by Folsome, et al., [7] using GC/MS, recent studies by Schwartz [11] and by Hayatsu, et al., [12] have shown that these constituents of the nucleic acids may indeed exist in the carbonaceous chondrites. 

Pyrimidinyl halides are not only precursors for Pd-catalyzed reactions, but also important pharmaceuticals in their own right. One of the most frequently employed approaches for halopyrimidine synthesis is direct halogenation. When pyrimidinium hydrochloride and 2-aminopyrimidine were treated with bromine, 5-bromopyrimidine and 2-amino-5-bromopyrimidine were obtained, respectively, via an addition-elimination process instead of an aromatic electrophilic substitution [4, 5], Analogously, 2-chloro-5-bromopyrimidine (1) was generated from direct halogenation of 2-hydroxypyrimidine [6], Treating 1 with HI then gave to 2-iodo-5-bromopyrimidine (2). In the preparation of 5-bromo-4,6-dimethoxypyrimidine (4), N-bromosuccinimide was found to be superior to bromine for the bromination of 4,6-dimethoxypyrimidine (3) [7]. 

We also enconnter tautomerism in hydroxy- and amino-diazines, and the preference for one tautomeric form over the other follows what we have seen with the pyridine derivatives. Thus, with the exception of 5-hydroxypyrimidine, all the mono-oxygenated diazines exist predominantly in the carbonyl tan-tomeric form. We term these amide-like tautomers diazinones. 5-Hydroxypyrimidine is analogous to 3-hydroxypyridine, in that the hydroxyl is wrongly positioned for tautomerism. 

A Princeton group announced the first synthesis of L-5-deazaFA (91) via a path which to date remains the shortest and most direct route to this series [79, 80], In one step, reaction of 2,4-diamino-6-hydroxypyrimidine (87a) with purified triformylmethane [81a,b] produced 2-amino-5-deazapterin-6-carbox-aldehyde (88a), which was characterized as the acetamide (89a). Reaction of (89a) with dimethyl p-aminobenzoyl-L-glutamate in glacial HOAc afforded an intermediate imine which was reduced in situ with borane-triethylamine, yielding (90). Saponification of the amide and esters then completed the synthesis of (91) in 62% yield from (88a) (Scheme 3.18). Adaptation of this... 

An early structural modification of FA and AP involved alkylation at C-9 and/or N-10. 10-MethylFA (447) [197] was prepared by reaction of 2,4,5-triamino-6-hydroxypyrimidine, 2,3-dibromopropionaldehyde and diethyl p-methylaminobenzoylglutamate (35), followed by alkaline hydrolysis (the Waller condensation). Analogous utilization of 2,2,3-trichlorobutyraldehyde and the requisite p-(JV-substituted amino)benzoylglutamate furnished (448a-c) (Scheme 3.88) [198]. The preparation of (450) by condensation of 2,4,5,6-tetraaminopyrimidine and the a-ketoacetal (449) was reported without details (Scheme 3.89) [199],... 

Heterocyclic coupling components that have been coupled with diazotized ami-nophenyltrimethylammonium chloride are l-alkyl-6-hydroxy-2-pyridone [93], 1-amino-3-hydroxy-isoquinoline [94], and 2,4-diamino-6-hydroxypyrimidine [95], The trialkylammoniumaryl residue may also be connected to the aromatic diazo component via a sulfone or a sulfonamido function [96], Disazo dyes in this series (e.g., 34) [77901-21-4] may also be generated from monoazo dyes that still contain a primary amino group by dimerization using phosgene [97] or cyanuric chloride [98],... 

Ethyl (8//)-pyrimido[5,4-fc][l,4]oxazine-6-carboxylate (187) could be obtained in about 82% yield by boiling 6-amino-4-chloro-5-hydroxypyrimidine (186) with ethyl 2-chloroacetoacetate in ethanol, i.e. triethylamine <73KGS1694>. 

Azine approach. 4-Amino-5-hydroxypyrimidine condenses with acid anhydrides or esters to form the corresponding 2-substituted oxazolopyrimidine system (77CPB491). Under relatively mild reaction conditions the nucleoside 6-amino-5-hydroxyuridine will undergo cyclocondensation with formamide under the influence of polyphosphate ester to form the oxazolo-fused nucleoside (230) both protected and non-protected pyrimidine nucleosides have been used in this reaction (73CPB1327). 

Diamino-6-hydroxypyrimidine condenses with nitromalonaldehyde in presence of alkali to give 2-amino-4-hydroxy-6-nitropyrido[2,3-d]pyrimi-dine (100) (75%).92 In a similar reaction 2,4-dioxo-l-hydroxy-6-nitro-lf/,3//-pyrido[2,3-d]pyrimidine is formed (101) [Eq. (32)].93... 

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